Microfluidics deals with the behavior, precise control and manipulation of small volumes of fluids that are typically constrained to micrometer-length scale channels and to volumes typically in the sub-milliliter range. Here, fluids refer to liquids and either term may be used interchangeably in the rest of the document. In particular, typical volumes of liquids in microfluidics range from 10-15 L to 10-5 L and are transported via microchannels with a typical diameter of 10-7 m to 10-4 m.
At the microscale, the behavior of the liquids can differ from that at a larger, macroscopic scale. In particular, surface tension, viscous energy dissipation and fluidic resistance are dominant characteristics of the flow. For example, the Reynolds number, which compares an effect of momentum of a fluid to the effect of viscosity, can decrease to such an extent that the flow behavior of the fluid becomes laminar rather than turbulent.
In addition, liquids at the microscale do not necessarily mix in the traditional, chaotic sense due to the absence of turbulence in low-Reynolds number flows and interfacial transport of molecules or small particles between adjacent liquids often takes place through diffusion. As a consequence, certain chemical and physical properties of liquids such as concentration, pH, temperature and shear force are deterministic. This provides more uniform chemical reaction conditions and higher grade products in single and multi-step reactions.
A microfluidic probe is a microfabricated scanning device for depositing, retrieving, transporting, delivering, and/or removing liquids, and in particular liquids containing chemical and/or biochemical substances. For example, the microfluidic probe can be used on the fields of diagnostic medicine, pathology, pharmacology and various branches of analytical chemistry. Here, the microfluidic probe can be used for performing molecular biology procedures for enzymatic analysis, deoxyribonucleic acid (DNA) analysis and proteomics.
Many of chemical and biochemical processes require multiple steps that are performed sequentially, involving exposure of a target surface to different liquids including (bio)chemicals, solvents and buffers under various conditions such as different temperatures, different concentrations and/or different durations.
Accordingly, the microfluidic probe should enable the delivery of a sequence of liquids in small volumes to a surface with low or no mixing between the sequential liquids. During transport of the liquids, these sequential sections of liquids inside a capillary or microfluidic channel are often termed as ‘plugs’. Typically, in microfluidic capillaries and channels, mixing between subsequent plugs containing different liquids due to (Taylor) dispersion decreases the concentration gradient between these subsequent plugs. In order to deliver a sequence of small-volume plugs to a surface, the microfluidic probe should be capable of rapidly switching between different liquids that form a sequence of small-volume plugs. In the meantime, the dispersion of plugs during the delivery to the surface should be limited in order to prevent subsequent plugs from mixing with one another.
Microfluidic probe heads are know which are suitable for patterning continuous and discontinuous patterns of biomolecules on surfaces and processing resist materials on a surface. However, liquids that are sequentially delivered to the target surface tend to mix with one another due to advective and diffusive effects. As a result, the sequence of plugs delivered to the surface may no longer be identical in terms of solute or particle concentration, viscosity and plug volume by the time it reaches the surface as compared to its initial state shortly after the point where the sequence is generated.
One approach to prevent sequentially delivered liquids from mixing with one another is made by inserting spacers of an immiscible-phase fluid between sequential plugs that have different continuous-phase liquids. For instance, the sequential plugs could be aqueous, while the immiscible-phase spacers are constituted by an oil or a gas. The immiscible-phase spacers prohibit a diffusion of solutes and/or particles between sequential plugs. “The chemistrode: A droplet-based microfluidic device for stimulation and recording with high temporal, spatial, and chemical resolution”, D. Chen et al., PNAS, 2008 (105), 16843-16848, discloses a tool that delivers aqueous stimulus plugs separated by segments of an immiscible phase to a target surface and retrieves response plugs. However, the tool and the immiscible-phase spacers come into direct contact with the target surface.
A drawback of many prior art solutions is that they are not applicable to local chemistry performed in wet environments, in particular when willing to use hydrodynamic flow confinement. Therefore, the deposition of droplets cannot be localized due to spreading of the liquid using this device and method.